Hepatocellular carcinoma (HCC) is a prevalent and highly malignant cancer throughout the world. Effective treatment of this disease is impeded by the high rate of metastasis, recurrence, and chemoresistance. Recent studies have revealed the close relationship between the malignant phenotype of HCC and cancer stem cells (CSCs). Therefore, CSC-targeted therapy is considered a promising strategy to eradicate HCC. Traditional Chinese medicine (TCM) can be effective in preventing recurrence and metastasis of some advanced HCC. A growing amount of literature has discovered that extracts or compounds derived from TCM exert an anti-CSC effect. This review introduces some formulas and chemical compounds derived from TCMs that have been reported to inhibit CSCs of HCC; these TCM-related drugs may help to provide an alternative approach to help manage cancers, especially for HCC which has a great potential of metastasis, recurrence, and chemoresistance.

In 2006, the Hepatology Committee of Chinese Association of Integrative Medicine issued the “Guidelines for the Prevention and Treatment of Liver Fibrosis with Integrated Traditional Chinese and Western Medicine.” In recent years, the fields of Chinese medicine, Western medicine, and integrative medicine have made rapid advances in basic and clinical research into chronic liver disease, and accumulated new evidence for the prevention and treatment of hepatic fibrosis. Therefore, in order to meet clinical needs, liver disease experts of integrated traditional Chinese and Western medicine were united to revise the previous guidelines in order to help physicians make correct and reasonable decisions in the diagnosis and treatment of hepatic fibrosis.

Background
Oral mucositis (OM) is one of the most common complications of mucotoxic cancer therapy. Mucositis induces clinically significant pain, increases the risk of infections and affects the patients’ quality of life.

Objective
This study investigated the effects of an herbal preparation from Plantago ovata hydrocolloid in the prevention and treatment of OM, in breast cancer patients undergoing chemotherapy with a regimen including adriamycin.

Design, setting, participants, and interventions
This research was a double-blind, randomized, controlled crossover trial. The herbal compound consisted of a mixture of 500 mg of P. ovate husk in 30 mL water plus three drops of vinegar per dose, which was used as a mouthwash. Phytochemical and physicochemical tests of the compound were also performed. Twenty-eight patients who developed mucositis during the chemotherapy screening cycle were randomized to the herbal compound (n = 14) and placebo (n = 14) groups. They received herbal compound or placebo three times per day during their next chemotherapy cycle (cycle 1 of treatment). Patients were crossed over during cycle 2 of treatment and received the alternative therapy. An oral care protocol was prescribed to all patients in cycles 1 and 2 of the treatment.

Main outcome measures
The patients were visited at baseline, the end of the first and second weeks of the screening cycle, and the end of the first and second weeks of each of two treatment cycles. The degree of mucositis was used as the main treatment outcome. Other indexes, such as the severity of pain, xerostomia grade and the quality of life were also measured.

Results
Compared with the placebo, the herbal compound significantly reduced the degree of mucositis, the severity of pain and the xerostomia grade; it also improved the patients’ quality of life (P < 0.05). Comparison between the screening cycle and placebo treatment group showed that the oral care protocol had a significant effect in the reduction of OM (P < 0.05).

Conclusion
The oral care protocol and the herbal compound based on P. ovata are effective ways for preventing and treating OM in patients undergoing mucotoxic cancer therapy.

Trial registration: Iranian registry of clinical trials IRCT20180923041093N1.

Objective
To examine the association between traditional Chinese medicine (TCM), preconception health patterns and fertility outcomes.

Methods
A community-based prospective cohort study was conducted in China. A total of 3012 newly married women who were willing to conceive within 2 years were enrolled in the study and took National Free Prepregnancy Checkups (NFPC). A reliably structured self-rating scale was used to measure the TCM preconception health patterns of the enrolled women. A 3-year follow-up was conducted to obtain the fertility outcomes, including pregnancy rate, time to pregnancy, spontaneous miscarriage and newborn status. Statistical analyses were conducted using Chi-square or Fisher’s exact tests, logistic regression models, general linear models and the Cox proportional hazard model.

Results
The fertility outcomes showed no statistic correlations to the terms of NFPC in this population. Approximately a half of the women (46.66%) had unhealthy patterns. Women with qi & blood-deficiency (odds ratio [OR] = 35.19, 95% confidence interval [CI] = 1.55–801.15) or qi-stagnation (OR = 4.55, 95% CI = 0.90–23.06) pattern took a longer time to get pregnant, and those with qi-stagnation (OR = 2.05, 95% CI = 1.1–3.82) or yang-deficiency (OR = 1.91, 95% CI = 1.12–3.25) pattern had a higher risk of spontaneous miscarriage.

Conclusion
Three unhealthy TCM patterns during the preconception period might be risk factors for low fecundity or poor pregnancy outcomes. The TCM preconception pattern identification may provide a convenient and effective way to screen for potential pregnancy risks beyond the NFPC. Further, appropriate interventions based on the TCM preconception health patterns are needed to improve quality in women’s fecundability and birth outcomes.

Objective 

The Lung-toxin Dispelling Formula No.1 (referred to as Respiratory Detox Shot, RDS) was established based on the theory of traditional Chinese medicine (TCM) medicinal properties and the classical prescription of TCM. It has demonstrated therapeutic benefits in both disease control and prevention in the effort to contain corona virus disease 2019 (COVID-19). However, the material basis and action mechanism of RDS are still unclear. The goal of the study is to clarify the material foundation and action mechanism of RDS.

Methods 

To achieve in-depth analyses of RDS from a holistic perspective, an integrative analytical platform was constructed, including target prediction, protein-protein interaction (PPI) network, cluster analysis, and the hub genes involved in the disease pathways were identified, and their corresponding compounds were further applied to molecular docking for in vitro biological validation. The presence of the validated compounds was also measured to demonstrate the material basis of RDS. In our network pharmacology study, a total of 26 bioinformatic software and databases were accessed, and 6 networks covering the entire Zang-fu viscera were constructed to achieve comprehensive analysis and visualization of the intricate connections among the compounds-targets-disease pathway-meridians of RDS.

Results 

For all 1071 compounds of 9 ingredients of RDS from established TCM databases, 157 compounds passed drug-likeness screening and led to 339 predicted targets in the compound-target network. 42 hub genes with core regulatory effects were extracted from the PPI network, and 134 compounds and 29 crucial disease pathways were implicated in the target-compound-disease network. Twelve disease pathways attributed to Lung-Large intestine meridian, with 6 and 5 to Kidney-Urinary bladder and Stomach-Spleen meridians, respectively. 118 candidate compounds showed a high binding affinity with SARS-CoV-2 3-chymotrypsin-like protease (3CL^pro) by molecular docking using computational pattern recognition. The in vitro activity of 22 compounds was validated by the 3CL^pro inhibition assay. Finally, using the technique of liquid chromatography mass spectrometry in data-independent analysis mode, 7 out of 22 compounds were confirmed and validated in RDS aqueous decoction with reference standards in both non-targeted and targeted approaches.

Conclusion 

Our results unveiled that RDS acts primarily in the Lung-Large intestine, Kidney-Urinary bladder, and Stomach-Spleen meridians, with other Zang-fu viscera strategically covered by all 9 ingredients. Integrated with the context of TCM meridian theory, multiple components and targets of RDS demonstrate the action dual effects of health-strengthening and pathogen-eliminating in one prescription to achieve systemic therapeutic effects for early COVID-19 control and prevention.

Objective:
The present work tested organic solvents to prepare an extract with anticancer properties from a polyherbal mixture containing Nigella sativa (seeds), Hemidesmus indicus (roots) and Smilax glabra (rhizomes). We evaluate anticancer effects in non-small-cell lung cancer cells (NCI-H292), and discuss optimization for pharmaceutical use in the context of efficacy, yield and toxicity.
Methods:
Using different organic solvents, six extracts were prepared from the polyherbal mixture. Based on the cytotoxic effects of these extracts on NCI-H292 cells and normal lung cells (MRC-5), as evaluated by the sulphorhodamine B assay, the total ethyl acetate (T-EA) extract was selected for further analysis. The possible anticancer mechanisms were assessed by evaluating the extract’s effects on apoptosis (through fluorescent microscopic analysis, DNA fragmentation analysis, caspase 3/7 assay and analysis of expression levels of apoptosis-related genes p53, Bax, survivin, Hsp70 and Hsp90), colony formation and antioxidant activity.
Results:
The extract had cytotoxic effects against NCI-H292 cells in a time- and dose-dependent manner. Significant antioxidant activity and inhibition of colony formation were also observed. The expression level of caspase 3/7 significantly (P ? 0.001) increased in NCI-H292 cells treated with 50 μg/mL of the extract. The same dosage led to a significant increase in expression levels of Bax and p53 (P ? 0.05 and P ? 0.01 respectively), accompanied by a significant decrease (P ? 0.0001) in survivin, Hsp 70 and Hsp 90.
Conclusion:
T-EA extract of the above polyherbal mixture has cytotoxicity against NCI-H292 cells via induction of apoptosis, antioxidant effects and inhibition of colony formation

Objective

To examine whether Caulerpa okamurae ethanolic extract (COE) could inhibit obesity-mediated inflammation, improve glucose metabolism and increases insulin sensitivity, using in vitro cell models of RAW 264.7 macrophages and 3T3-L1 adipocytes. 

Methods

We cocultured 3T3-L1 adipocytes in direct contact with lipopolysaccharide-stimulated RAW 264.7 macrophages and induced insulin resistance in 3T3-L1 adipocytes with tumor necrosis factor-α (TNF-α) in the presence or absence of 250 μg/mL of COE. We investigated various markers of inflammation, glucose regulation and insulin sensitivity in these models using Griess reagent to measure nitric oxide (NO) production, 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl) amino]-2-deoxyglucose to measure glucose uptake, Western blot analysis to quantify protein expression and reverse transcriptase-polymerase chain reaction to evaluate mRNA expression.

Results

We found that COE (250 μg/mL) significantly inhibited the lipopolysaccharide-induced inflammatory response in RAW 264.7 macrophages by downregulating NO production, nitric oxide synthase 2 expression and nuclear translocation of nuclear factor-κB. COE also showed similar anti-inflammatory activity in coculture, along with decreased TNF-α, interleukin-6 and monocyte chemoattractant protein mRNA expression. In addition, COE also improved glucose uptake in coculture by upregulating glucose transporter-4 (GLUT-4) and adiponectin and reducing serine phosphorylation of insulin receptor substrate-1 (IRS1). In the TNF-α-induced insulin resistance model of 3T3-L1 adipocytes, COE significantly improved both basal and insulin-stimulated glucose uptake, accompanied by phosphorylation of IRS1 at tyrosine 632, phospho-5' adenosine monophosphate-activated protein kinase α and glycogen synthase kinase-3β (Ser9) as well as upregulation of GLUT-4.

Conclusion

Together, these findings suggest that COE has potential to treat or prevent obesity-induced metabolic disorders.

Objective
In traditional medicine, the seeds of Thai Mucuna pruriens (T-MP) are used to treat male dysuria and are believed to enhance fertility. However, information pertaining to the toxicity of T-MP and its interaction with other properties is limited. This study was thus conducted to evaluate the antioxidant capacity and subacute toxicity of T-MP in the reproductive system.

Methods
Total phenolic content and antioxidant capacity of T-MP seed extract were determined using total phenolic content, 2,2-diphenyl-1-picrylhydrazyl and ferric reducing antioxidant power assays. Male and female adult rats were treated orally with T-MP at a dosage of 150 or 300 mg/kg body weight for 14 consecutive days. Sex hormones and functional parameters in the liver and kidney were evaluated. Histopathology of all tissue was conducted using Masson’s trichrome staining. Sperm parameters, including concentration, morphology, acrosome reaction status and DNA damage, were also examined. Expression of tyrosine phosphorylated protein (TyrPho), androgen receptor and A-kinase-anchoring protein 4 (AKAP4) were investigated using the Western blot technique.

Results
T-MP seed extract contained phenolic compounds and exhibited high antioxidant capacity with no toxicity at the tested doses. It did not affect liver or kidney function parameters in the male rats, but increased estradiol, aspartate aminotransferase and alanine aminotransferase levels in the females. Additionally, it decreased serum progesterone and alkaline phosphatase levels in female rats. Serum and intratesticular testosterone levels were significantly lower in male rats that received a high dosage of T-MP. Histopathological changes were not observed in any tissue treated with T-MP. T-MP also significantly increased sperm concentration (but did not affect sperm parameters), and enhanced testicular TyrPho protein and androgen receptor and expression of AKAP4 in sperms.

Conclusion
T-MP seed extract exhibited antioxidant capacity and was not harmful to reproductive tissues. It also had a phytoestrogenic effect on females and increased the expression of testicular and sperm markers of male fertility.